The nature of the in vivo covalent binding of H3-dioxane in the carcinogenicity target tissues will be studied. Since binding of dioxane in vitro to DNA does not appear to be catalyzed by microsomes in the presence of NADPH, it will be investigated if certain oxidative byproduct(s) formed during microsomal electron transport may play a role in the in vivo binding. The possibility will be explored that the in vivo tissue binding of dioxane is catalyzed by a mixed-function oxidase in the nuclear membrane rather than in the endoplasmic reticulum. The structure of the chemically reactive form responsible for the in vivo binding will be investigated. In bioassay studies the carcinogenicity of structural analogs of dioxane will be studied.